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ID 115224
著者
Miyakawa, Kei Yokohama City University
Matsunaga, Satoko Yokohama City University
Yokoyama, Masaru National Institute of Infectious Diseases
Kimura, Yayoi Yokohama City University
Nishi, Mayuko Yokohama City University
Kimura, Hirokazu Gunma Paz University
Sato, Hironori National Institute of Infectious Diseases
Hirano, Hisashi Yokohama City University
Tamura, Tomohiko Yokohama City University
Akari, Hirofumi Kyoto University
Miura, Tomoyuki Kyoto University
Sawasaki, Tatsuya Ehime University
Yamamoto, Naoki National Institute of Infectious Diseases|Tokyo Medical and Dental University
Ryo, Akihide Yokohama City University
資料タイプ
学術雑誌論文
抄録
Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response.
掲載誌名
Nature Communications
ISSN
20411723
cat書誌ID
AA12645905
出版者
Springer Nature
10
開始ページ
1844
発行日
2019-04-23
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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言語
eng
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出版社版
部局
医学系